The goal of this investigation is to determine the role of oxygen-derived free radicals in aging of the brain. This goal will be approached by obtaining measurements of the effect of age on different aspects of free formation and metabolism in several areas of monkey brain. The parameters to be measured include lipid peroxidation, activity of superoxide dismutase, glutathione peroxidation, and catalase, concentrations of free radical scavengers including glutathione, ascorbic acid and uric acid, and the ability of brain supernatant to inhibit free radical formation. Our method of scavenger measurement, HPLC with coulometric detection using a 16 channel detector system, will allow us to determine simultaneously concentrations of monoamines, their precursors and metabolites in the same tissue sample. Additional information on the activity of selected neurotransmitter systems will be obtained by the measurement of choline acetyltransferase activity and GABA concentrations. Relationship between free radical metabolism and neurotransmitter levels will be explored. In addition, all variables measured in this project will be correlated with behavioral, biochemical and morphological age-related changes found in the same monkeys.